目的 建立维生素B2不同晶型状态的检测方法,并对不同晶型的水分吸附特性进行研究。方法 采用粉末X射线衍射技术(p-XRD)、差示扫描量热技术(DSC)和红外光谱分析技术(IR)对维生素B2两种晶型状态进行了表征,采用动态水分吸附分析技术(DVS)对两种晶型的水分吸附特性进行了深入研究,同时考察了温度、湿度和光线对其晶型转化的影响。结果 经鉴定,国内外两批维生素B2为不同晶型,分别为无水物Ⅰ型和一水合物,无水物Ⅰ型在二甲基亚砜中结晶会转化为一水合物。一水合物有引湿性,在不同相对湿度条件下结晶水的数量可能发生变化,温度对一水合物水分吸附曲线的影响较大;无水物Ⅰ型结晶程度高,几乎不引湿,不同温度下水分吸附数据显现的变化很小。结论 获得了对维生素B2晶型物质的有效鉴别分析方法,确定了维生素B2的无水物Ⅰ型相比一水合物更稳定,证实了动态水分吸附分析法可作为药物多晶型研究的有效手段。
Abstract
OBJECTIVE To establish the detection technology of riboflavin polymorphism, and investigate the moisture sorption properties of riboflavin. METHODS The two crystal forms of riboflavin were characterized by different analysis methods, such as powder X-ray diffraction method (p-XRD), differential scanning calorimetry method (DSC) and infrared spectrum method (IR). Dynamic vapor sorption (DVS) analysis was adopted to acquire moisture sorption dynamics of the two crystal forms. The influences of temperature, humidity and light on crystal transformation were explored. RESULTS The crystal forms of two batches of riboflavin samples were identified as anhydrate Ⅰ and monohydrate, respectively. The monohydrate could be obtained by recrystallizing in DMSO. The monohydrate was hygroscopic, the number of crystal water may change at different relative humidities, and the moisture sorption dynamics of the monohydrate was greatly influenced by temperature. The anhydrate Ⅰwas almost non-hygroscopic, and temperature hardly affected its moisture sorption dynamics. CONCLUSION Characteristic data for riboflavin polymorphism are obtained, and the results show that anhydrate Ⅰ is more stable than monohydrate. This study indicates that DVS could be used in studies on drug polymorphism.
关键词
维生素B2 /
多晶型 /
X射线衍射 /
热分析 /
红外 /
动态水分吸附 /
水分吸附动力学曲线 /
吸附-解吸附等温线
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Key words
riboflavin /
polymorphism /
XRD /
thermal analysis /
IR /
DVS /
moisture /
sorption dynamics /
adsorption-desorption isotherm
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中图分类号：
R917
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参考文献
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脚注
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基金
国家科技重大专项“重大新药创制”资助项目(2015ZX09303001);中国食品药品检定研究院中青年发展研究基金资助项目(2010A3,2013NA3)
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